Phase 3 data reinforce ianalumab activity in Sjögren’s disease

Ianalumab, a monoclonal antibody that depletes B cells through enhanced antibody-dependent cellular cytotoxicity and separately inhibits their activation through B-cell activating factor (BAFF), showed significant improvement in disease activity versus placebo in participants with Sjögren’s disease, according to phase 3 clinical trial data.

Prof. Thomas Grader-Beck (Johns Hopkins University of Medicine, MA, USA) presented the results from the NEPTUNUS-1 (NCT05350072) and NEPTUNUS-2 (NCT05349214) global, randomised, placebo-controlled trials in participants with active Sjögren’s disease [1]. The treatment consisted of subcutaneous ianalumab 300 mg monthly or placebo for 52 weeks in both trials, with an additional ianalumab 300 mg every 3 months arm in NEPTUNUS-2. Adults were eligible if they satisfied 2016 ACR/EULAR classification criteria, had a diagnosis ≤7.5 years prior, an EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ≥5, and a stimulated whole salivary flow rate of ≥0.05 mL/min. The primary endpoint was the change from baseline in ESSDAI at week 48. Overall, 275 and 504 participants were randomised in NEPTUNUS-1 and -2, respectively.

The primary endpoint was met in both trials, demonstrating the superiority of ianalumab over placebo. Ianalumab 300 mg monthly compared with placebo led to a mean difference in change from baseline in ESSDAI of -1.3 (95% CI -2.6 to 0.0; P=0.0496) in NEPTUNUS-1 and -1.0 (95% CI -2.0 to 0.0; P=0.041) in NEPTUNUS-2. Numerical improvements versus placebo were also observed with ianalumab 300 mg every 3 months, but they did not reach statistical significance.

Overall, infection rates were similar across treatment arms. One malignancy was reported with placebo and none with ianalumab in NEPTUNUS-1, while 4 malignancies were reported with ianalumab and none with placebo in NEPTUNUS-2.

“NEPTUNUS-1 and -2 are the first global, replicate, phase 3 studies in Sjögren’s disease to meet their primary objective, showing a statistically significant improvement in ESSDAI,” concluded Prof. Grader-Beck. He added that “ianalumab 300 mg monthly demonstrated a favourable safety profile, supporting a positive risk-benefit profile in Sjögren’s disease.”

1. Grader-Beck T, et al. Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren’s disease: Efficacy and safety results from two global Phase 3, randomized, placebo-controlled double-blind studies (NEPTUNUS-1 and NEPTUNUS-2). ACR Convergence, 24–29 October 2025, Chicago, IL, USA.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 30 October 202530 October 2025